CN110997074A

CN110997074A - Topical compositions for anti-aging benefits

Info

Publication number: CN110997074A
Application number: CN201880053224.5A
Authority: CN
Inventors: P·M·迪亚斯; V·R·加德吉; N·贾格迪什
Original assignee: Unilever PLC
Current assignee: Unilever IP Holdings BV
Priority date: 2017-08-17
Filing date: 2018-07-16
Publication date: 2020-04-10
Also published as: WO2019034347A1; EP3668608A1; MX2020001745A; US20200253860A1

Abstract

Disclosed herein are topical compositions comprising: (i) a first extract comprising a plant active extracted from emblic leafflower fruit (Emblica officinalis); and (ii) a second extract comprising a volatile plant active extracted from tea (Camellia sinensis), wherein the second extract comprises E-2-hexenal and linalool in a ratio of 0.1:1 to 10:1 parts by weight. Also disclosed are methods of activating Nrf2, up-regulating gene expression of HO1 in melanocytes, and up-regulating gene expression of NQO1 in fibroblasts, comprising the step of applying the topical cosmetic composition of the first aspect.

Description

Topical compositions for anti-aging benefits

Technical Field

The present invention relates to topical compositions for activating Nrf2 in certain human cells. Activation of Nrf2 is critical for anti-aging benefits.

Background

Human skin consists of two important layers: a thicker layer called the dermis and a thinner layer called the epidermis located above it. The dermis is responsible for strength, elasticity and thickness. As aging progresses, the thickness of this layer decreases, which is believed to be partly responsible for the appearance of wrinkles in aging skin. The epidermis is composed of a variety of cells that provide elastic and barrier properties. Keratinocytes account for 75-80% of the total number of cells in the epidermis. Within the epidermis, keratinocytes are present in four distinct differentiation stages. This differentiation is essential for certain essential functions of the skin, namely for a protective barrier against environmental factors and for preventing loss of body water. Skin is composed primarily of three major types of cells, which are keratinocytes, melanocytes, and fibroblasts.

Phase 2 enzymes (Phase-2 enzymes) are the major detoxifying enzymes and are an important part of the cellular defense against oxidants and other toxic chemicals.

While each individual 2-phase gene may be regulated by a variety of mechanisms, common to many 2-phase genes is the Keap1-Nrf2-ARE signaling system. Nrf2, nuclear factor erythroid 2-related factor 2, is a transcription factor normally sequestered by its repressor, Keap 1. Binding to Keap1 promoted proteasomal degradation of Nrf 2. Dissociation of Nrf2 from Keap1 allows the former to heterodimerize (heterodimerize) with a partner (partner), bind to cis-acting DNA regulatory elements, and promote transcription of downstream genes. DNA regulatory elements bound and activated by Nrf2 heterodimers ARE called Antioxidant Response Elements (AREs). One or more copies of a typical ARE sequence ARE known to be present in the 5' -flanking region of the 2-phase gene, including HO-1.

Each cell type plays a unique role in the appearance and health of the skin, either by itself or in view of interactions with other types. The nuclear factor erythroid 2-related factor 2(Nrf2) is a major regulator of the skin's response to oxidative stress, which serves as a protective mechanism. Nrf2 regulates downstream expression of various enzymes that regulate antioxidant and detoxifying mechanisms. Therefore, chemical agents that induce activation of Nrf2 are commonly used as screens (screens) to identify active substances suitable for various skin benefits, including inhibition of melanin synthesis in melanocytes and inhibition of reactive oxygen species in fibroblasts and keratinocytes.

Herbal extracts are known for their detoxification effects, and certain extracts are known to upregulate Nrf2 expression. The potential of herbal medicine can now be determined by using high throughput screening based on Antioxidant Response Element (ARE) cell lines. Some herbs induced partial activation of Nrf2, which could be of the order of 2 to 3 fold increase.

WO14095198 a1(Unilever) discloses the use of an extract of tea (camellia sinensis) in a cosmetic composition for enhancing the immunity of the skin.

WO13060710 a2(Unilever) discloses topical cosmetic compositions containing a selected ratio of green tea extract and black tea extract for anti-inflammatory benefits.

US 5306486A (Unilever, 1994) discloses cosmetic compositions comprising green tea and a sunscreen compound. The composition blocks ultraviolet radiation.

US2005/0084566 a1(Bavan) discloses a process for producing instant tea soluble in hot water comprising the steps of: (a) forming an extract by treating black tea leaves with hard warm water, (b) stripping its extract of aroma volatiles by passing the tea extract through a flash evaporator under partial vacuum, (c) separating at least 12% by weight of insoluble solids from the extract by subjecting the extract to repeated clarification and polishing to obtain a clarified concentrate, (d) separating 6-10% of soluble solids from the clarified concentrate, (e) adjusting the pH of the concentrate to neutral by adding a food acid, (f) adding the aroma volatiles obtained in step (b) to the concentrate, and (g) obtaining a substantially moisture free tea powder which can be reconstituted in hot water to produce an instant tea substantially free of haze and cloudiness. In this process, aroma is added back to the concentrate that is free of insoluble material and the process involves the production of hot water soluble instant tea, which is known to be substantially free of hot water insoluble tea solids.

US2007/0160737 a1 (uniliqua) discloses a process for manufacturing an aromatic green tea product for consumption as a beverage, comprising the steps of: providing a fragrance composition comprising t-2-hexenal and linalool in a weight ratio of at least 0.7:1, and combining the fragrance composition with a tea product.

CN 102091006A (Long Run Tea Group, 2011) discloses a facial cleanser comprising 5-20 wt% of Tea extract, 5-20 wt% of coenzyme Q10, 5-20 wt% of juice of emblic leafflower fruit (emblic leafflower) and other substances. The cleanser is said to provide ultraviolet resistance, oxidation resistance, pore shrinkage, antibacterial, anti-acne, degreasing, radiation resistance, anti-allergy, removal of excess fat, moisturization, anti-aging, improvement of smoothness and elasticity, wrinkle and fine groove prevention, and free alkali removal; and it is said that skin immunity is enhanced after long-term use, thereby protecting skin in harmful environments.

US20080050459 a1(3Lab Inc) discloses a cosmetic formulation comprising an effective amount of an extract of the fruit of emblica officinalis (Phyllanthus emblica) and at least one oligopeptide such as oligopeptide-4 and oligopeptide-5 (tropoelastin oligopeptides), which may further comprise licorice extract and α -arbutin.

Adhikari et al have disclosed in the International Journal of Cosmetic Science,2008,30,353-360 that herbal extracts, such as Phyllanthus emblica and tea, have the ability to inhibit tyrosinase activity, but this activity is rated less than 50% of that of other herbs, such as Glycyrrhiza glabra and Morus alba.

Chaudhuri et al discuss the inhibitory effect of tannins contained in Phyllanthus emblica on melanin synthesis in Cosmetics & Toiletries 122(2007), pp.73-80.

Disclosure of Invention

Plant extracts of plants are widely used in cosmetic and pharmaceutical compositions. Typically, they are used in combination, i.e. as separate or mixed extracts of two, three, four or even more plants. Most of the time, the extracts exert their own effect, e.g. an extract of the root of plant X moisturizes the skin, while an extract of the leaf of another plant Y increases the skin elasticity. Very few extracts are known to interact with each other to provide a completely new effect or more than the sum of their individual effects.

We have surprisingly observed a synergistic interaction between plant extracts of a first plant, phyllanthus emblica, and a second plant, tea, under in vitro test conditions. The extracts interact synergistically, which manifests itself by activating Nrf2 or its downstream genes of at least one of fibroblasts or melanocytes.

According to a first aspect, a topical composition is disclosed comprising:

(i) a first extract comprising a plant active extracted from phyllanthus emblica; and

(ii) a second extract comprising volatile plant actives extracted from tea,

wherein the second extract comprises E-2-hexenal and linalool in a ratio of 0.1:1 to 10:1 by weight parts.

According to a second aspect, there is disclosed the use of a topical composition of the first aspect for activating Nrf 2.

According to a third aspect, there is disclosed the use of a topical composition of the first aspect for up-regulating the gene expression of heme oxygenase 1(HO-1) in melanocytes.

According to a fourth aspect, there is disclosed the use of a topical composition of the first aspect for up-regulating gene expression of NQO1 in fibroblasts.

According to a fifth aspect, there is disclosed a method of activating Nrf2 comprising the step of applying the topical cosmetic composition of the first aspect.

According to a sixth aspect, a method of up-regulating the gene expression of HO1 in melanocytes is disclosed, comprising the step of administering the topical composition of the first aspect.

According to a seventh aspect, there is disclosed a method of up-regulating gene expression of NQO1 in fibroblasts, comprising the step of administering the topical composition of the first aspect.

According to another aspect, a topical composition of the first aspect is disclosed for activating Nrf 2.

According to another aspect, a topical composition of the first aspect is disclosed for use in up-regulating gene expression of HO1 in melanocytes.

According to another aspect, topical compositions for up-regulating gene expression of NQO1 in fibroblasts are disclosed.

According to another aspect, there is disclosed the use of a first extract comprising plant actives extracted from emblica officinalis and a second extract comprising volatile plant actives extracted from tea in the manufacture of a topical composition for activating Nrf2, wherein the second extract comprises E-2-hexenal and linalool in a ratio of 0.1:1 to 10:1, parts by weight of the extracts.

According to another aspect, there is disclosed the use of a first extract comprising a plant active extracted from emblica officinalis and a second extract comprising a volatile plant active extracted from tea in the manufacture of a topical composition for up-regulating gene expression of HO1 in melanocytes, wherein the second extract comprises E-2-hexenal and linalool in a ratio of 0.1:1 to 10:1, parts by weight of the extracts.

According to another aspect, there is disclosed the use of a first extract comprising a plant active extracted from emblica officinalis and a second extract comprising a volatile plant active extracted from tea in the preparation of a topical composition for upregulating gene expression of NQO1 in fibroblasts, wherein the second extract comprises E-2-hexenal and linalool in a ratio of 0.1:1 to 10:1, parts by weight of the extracts.

Detailed Description

These and other aspects, features and advantages will become apparent to those of ordinary skill in the art upon review of the following detailed description and appended claims.

Numerical ranges expressed in the form "x to y"/"x-y" are understood to include x and y. When multiple preferred ranges are described in the form of "x to y"/"x-y" for a particular feature, it is to be understood that all ranges combining the different endpoints are also contemplated.

As used herein, the term "comprising"/"including" encompasses the terms "consisting essentially of … …" and "consisting of … …". Where the term "comprising"/"including" is used, the listed steps or options need not be exhaustive. Unless otherwise indicated, numerical ranges expressed in the form of "x to y"/"x-y" are understood to include x and y. In specifying any range of values or amounts, any particular upper value or amount can be associated with any particular lower value or amount. Except in the examples and comparative examples, or where otherwise explicitly indicated, all numbers are to be understood as modified by the word "about". All percentages and ratios contained herein are by weight unless otherwise indicated. As used herein, the indefinite article "a" or "an" and its corresponding definite article "the" mean at least one or more unless specified otherwise. Various features of the invention mentioned in the preceding individual sections are, where appropriate, applicable to other sections (mutatis mutandis). Thus, features specified in one section may be combined with features specified in other sections as appropriate. Section headings are added for convenience only and are not intended to limit the disclosure in any way.

Phyllanthus emblica fruit

Emblic leafflower fruit (Amla) is an ayurvedic herb. It is the fruit of the plant Phyllanthus Emblica (Emblica officinalis), also known as Phyllanthus Emblica (Phyllanthus Emblica). The fruit is also known as currant. The plant is a member of the euphorbiaceae, growing to medium-sized trees, which are found in the plain and pre-mountain areas throughout the indian subcontinent. It is used in many edible herbal preparations and in cosmetic compositions. Hereinafter, the source and the production place of the extract of emblic leafflower fruit are described in detail.

Preferably, the plant active from emblica officinalis is extracted from its root, stem, leaf or bark by hydroalcoholic extraction. Preferably the first extract comprises more than 5 wt% ellagic acid, based on the weight of the extract. In addition, the extract also contains vitamin C. Such extracts are commercially available from a supplier named Phyto Life Sciences Pvt Ltd, India under the website http:// www.plpl.in/herbal-extract-India.

The first extract is used as an ingredient in the composition of the present invention. Preferably, the topical composition of the present invention comprises botanical actives extracted from phyllanthus emblica in an amount of 0.001 to 10% by weight of the first extract.

Tea

The compositions of the present invention comprise a volatile plant extract from tea, which is a tea plant. The plant is Chinese tea (Camellia sinensis var. sinensis). Alternatively, it is assamica tea (Camellia sinensis). Alternatively, the volatile plant extract is obtained from a combination of the above two varieties.

Preferably the volatile botanical active from tea is extracted from its leaves or fibres or the active is contained in a fraction obtained by vacuum stripping, steam distillation or fractionation of the volatile botanical active.

A preferred process for preparing volatile plant actives from tea is as follows:

the method comprises a first step of pressing juice from fresh leaves of the plant. This step leaves a residue of the pressed leaves. The residue was dried in a desiccator. This step results in a dried leaf residue and a dryer exhaust rich in aroma compounds. The aromatic compounds are recovered from the exhaust as aromatic condensate. More details of this process can be found in US 2007/0160737A 1 (Unilever).

Preferably, the aromatic condensate is distilled to concentrate it. The aroma condensate is a volatile plant active extracted from tea. The actives comprise E-2-hexenal and linalool in a ratio of 0.1:1 to 10:1 by weight parts.

Preferably the ratio is from 0.1:1 to 5: 1. In addition to the two components mentioned above, the extract preferably comprises a further volatile component, namely methyl salicylate. The volatile extract of tea differs from various other extracts reported elsewhere in the specific ratio of the two important components present therein. Preferably the volatile botanical active extracted from tea comprises greater than 80 wt% volatile ingredients, more preferably greater than 90 wt% and still more preferably greater than 95 wt% volatile ingredients. Another difference is that the extracts reported elsewhere are usually extracts containing a large amount of non-volatile components. Some other prior art compositions containing tea extract contain volatile as well as non-volatile components, where one or both components are absent or in a completely different ratio.

Preferably the composition of the invention comprises volatile plant active extracted from tea in an amount of 0.001 to 10% by weight of the second extract.

Further details of the compositions of the invention

As used herein, "topical composition" is intended to include compositions for application to an external surface (e.g., mammalian, especially human, skin) for better skin health benefits. Further preferably, the composition of the present invention is a cosmetic composition. It is further preferred that the compositions of the present invention are leave-on or rinse-off compositions, preferably leave-on compositions, and include any product that is primarily applied to the human body for the purpose of enhancing skin health but may also be used for the purpose of improving appearance, cleansing, odor control, or general aesthetics. As used herein, "skin" is intended to include skin on the face and body (e.g., neck, chest, back, arms, underarms, hands, legs, buttocks, and scalp) and especially to mean the face around the eyes (under-eye). The topical compositions of the present invention are particularly useful for application to areas of the skin where wrinkles are present or are more likely to be present, especially where the body is exposed to the sun.

The compositions of the present invention may be in the form of a liquid, lotion, cream, foam, scrub, gel, soap bar or toner, or applied with a device or via a mask, pad or patch. Non-limiting examples of skin compositions include leave-on skin lotions and creams, hair shampoos, hair conditioners, body washes, toilet bars (toilette bars), antiperspirants, deodorants, depilatories, lipsticks, foundations, mascaras, sunless tanners, and sun blocks.

The compositions of the present invention may be prepared according to the usual manner of preparing such compositions. Reference may be made to standard textbooks and formula guidelines.

When the cosmetic composition is a cosmetic composition, it preferably comprises a base, preferably a skin/cosmetically acceptable carrier. The carrier acts as a diluent, dispersant or carrier. Carriers may include materials commonly used in skin compositions such as water, liquid or solid emollients, propellants, powders, emulsifiers, solvents, humectants, thickeners. The carrier in the compositions of the invention is a single vehicle or a mixture of one or more vehicles. Preferably the carrier is present in the skin composition at from 80 wt% to 99 wt%, preferably from 85 wt% to 90 wt%.

The compositions of the present invention may also comprise a cosmetically acceptable carrier. Water is the most preferred carrier. The amount of water may be, for example, 1 to 99% by weight, preferably 5 to 90% by weight, more preferably 35 to 70% by weight, most preferably 40 to 60% by weight of the cosmetic composition. Typically the composition will be an oil-in-water emulsion, which in some embodiments may be an oil-in-water emulsion. Preferred emulsions are of the water-in-oil variety.

Where the carrier is an emulsion, it is preferred that the particles are dispersed in the oil phase of an aqueous-oil emulsion, as this may improve the stability of the dye in the composition.

Emollient materials may be included as carriers in the compositions of the present invention. These may be in the form of silicone oils, synthetic esters and/or hydrocarbons. The amount of emollient can be, for example, in any range/value from about 0.1% to about 95%, more preferably from about 1% to about 50%, by weight of the composition.

Silicone oils can be divided into volatile and non-volatile classes. As used herein, the term "volatile" refers to those materials that have a measurable vapor pressure at ambient temperature (25 ℃). The volatile silicone oil is preferably chosen from cyclic polydimethylsiloxanes (cyclomethicones) or linear polydimethylsiloxanes containing from 3 to 9, preferably from 4 to 5, silicon atoms. In many compositions of the invention in the liquid state, the volatile silicone oil as a carrier may form a relatively large component of the composition. Amounts may range, for example, from 5 to 80% by weight of the composition, more preferably from 20 to 70% by weight.

Non-volatile silicone oils useful as emollient materials include polyalkylsiloxanes, polyalkylarylsiloxanes, and polyether siloxane copolymers. The substantially non-volatile polyalkylsiloxanes useful herein include, for example, polydimethylsiloxanes. Preferred non-volatile emollients useful in the compositions of the present invention include polydimethyl siloxanes.

The organopolysiloxane crosslinked polymer can be effectively used. Representative of these materials are dimethicone/vinyl dimethicone crosspolymer and dimethicone crosspolymer available from a number of suppliers including Dow Corning (9040, 9041, 9045, 9506 and 9509), General Electric (SFE 839), ShinEtsu (KSG-15, 16 and 18[ dimethicone/phenyl vinyl dimethicone crosspolymer)]) And grant industries (

Brand materials) and lauryl/vinyl dimethicone crosspolymers, all of which are supplied by Shin Etsu (e.g., KSG-31, KSG-32, KSG-41, KSG-42, KSG-43, and KSG-44). The amount of silicone elastomer (when present) described above will generally be from 0.1 to 20% by weight, typically dissolved in a volatile silicone oil such as cyclomethicone.

When the polysiloxane is present in large amounts as a carrier and water is also present, the system may be oil continuous. These will typically require the use of a water-in-oil emulsifier such as dimethicone copolyol (e.g. dimethicone copolyol)

EM-90, which is cetyl dimethicone copolyol).

Ester emollients include:

a) alkenyl or alkyl esters of fatty acids having 10 to 20 carbon atoms. Examples thereof include isoeicosyl neopentanoate, isodecyl neopentanoate, isononyl isononanoate, cetyl ricinoleate, oleyl myristate, oleyl stearate and oleyl oleate.

b) Ether-esters such as fatty acid esters of ethoxylated fatty alcohols.

c) A polyol ester. Butylene glycol, ethylene glycol mono and di-fatty acid esters, diethylene glycol mono and di-fatty acid esters, polyethylene glycol (200-. Particularly useful are the pentaerythritol, trimethylolpropane and neopentyl glycol esters of C1-C30 alcohols. An example is pentaerythritol tetraethylhexanoate.

d) Wax esters such as beeswax, whale oil wax and wasabi wax.

e) Sterol esters, an example of which is cholesterol fatty acid esters.

f) Fatty acid sugar esters such as sucrose behenate and sucrose polygossypolate.

It is also particularly useful to

Brand marketed benzoic acid C_12-15An alkyl ester.

Hydrocarbons which are suitable cosmetically acceptable carriers include petrolatum, mineral oil, C₁₁-C₁₃Isoparaffins, poly α olefins, and especially isohexadecane, are useful as

101A is commercially available from Presperse Inc.

The polyhydric alcohol-type humectant may be used as a cosmetically acceptable carrier. Typical polyhydric alcohols include polyalkylene glycols, and more preferably alkylene polyols and their derivatives, including propylene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol and derivatives thereof, sorbitol, hydroxypropyl sorbitol, hexylene glycol, 1, 3-butylene glycol, isoprene glycol, 1,2, 6-hexanetriol, glycerol, ethoxylated glycerol, propoxylated glycerol and mixtures thereof. The humectant amount may be in any range/value from 0.5 to 50 weight percent of the composition, more preferably from 1 to 15 weight percent. Most preferred is glycerol (also known as glycerin). The amount of glycerol may range from 1% to 50% by weight of the composition, more preferably from 10 to 35% by weight, optimally from 15 to 30% by weight.

In addition to cosmetically acceptable carriers, the compositions of the present invention may contain a variety of other functional ingredients the sunscreen actives may be included in the compositions of the present invention, these may be organic compounds having at least one chromophore which absorbs ultraviolet light of 290 nm;. the chromogenic organic sunscreens may be divided into the following classes (with specific examples) including p-aminobenzoic acid, its salts and derivatives (ethyl, isobutyl, glyceryl esters; p-dimethylaminobenzoic acid), aminobenzoates (o-benzoates; methyl, menthyl, phenyl, benzyl, phenethyl, linalyl, terpinyl and cyclohexenyl esters), salicylates (octyl, pentyl, phenyl, benzyl, menthyl, glyceryl and dipropylene glycol esters), cinnamic derivatives (menthyl and benzyl esters, α -phenylcinnamoyl nitrile; butylcinnamoyl pyruvate), dihydroxycinnamic derivatives (umbelliferone, methylumbelliferone, methylacetophenone), trihydroxy derivatives (esculetin, methylesculetin, daphnetin, and glycoside esculin) and reslurin, as well as the salts of diphenyl butadiene, vinyl benzophenone, dibenzylidene and butyrophenone, and 2-4-benzoylideneacetophenone, 4-benzoylbenzophenone, 4, 4-and 4-benzoylbenzoic acid, 4-2-methoxybenzophenone, 4, 4-and 7-4-benzoylbenzoic acid, 2-4-methoxybenzophenone, 4, 4-and 7-4-methyl-4-or-methoxybenzophenone, 4-phenyl-4-or-phenyl-4-phenyl-methyl-4-phenyl-ethyl-phenyl-4-benzoic acid, 4-phenyl-ethyl benzoate, 4-and-phenyl-benzoic acid, 4-and-propyl-benzoyl-and-benzoic acid, 4-ethyl-and-4-propyl-benzoic acid, 4-and-propyl-4-phenyl-4-phenyl-propyl-phenyl-4-benzoic acid, and-propyl-benzophenone-and-benzophenone, and-4-benzophenone, and-4-benzophenone, and-benzophenone, and a-4-benzoic acid, and a-4-benzoic acid, and-benzophenone, and a-4-benzoic acid, and a mixture, a-benzoic acid, a mixture, a-benzoic acid, a mixture, a salt, a salt of a, a salt, a mixture, a salt of a, a.

Particularly preferred are materials such as Parsol

Obtainable ethylhexyl p-methoxycinnamate as Parsol

Avobenzone, Dermablock, available

(octyl salicylate) and Mexoryl

(INCI name is p-xylylene dicamphor sulfonic acid). The amount of organic sunscreen may be, for example, from 0.1 to 15% by weight of the composition, more preferably from 0.5% to 10% by weight, optimally from 1% to 8% by weight.

Various thickeners may be included in the composition. Illustrative but non-limiting examples are stearic acid, acrylamide/sodium acryloyldimethyl taurate copolymer (Aristoflex)

) Hydroxyethyl acrylate/acryloyl dimethyltauroSodium copolymer, aluminum starch octenyl succinate, and polyacrylate (such as carbomer, including

980、

1342、Pemulen

And

thickeners), polysaccharides (including xanthan gum, guar gum, pectin, carrageenan, and sclerotium gum), cellulose (including carboxymethyl cellulose, ethyl cellulose, hydroxyethyl cellulose, and methyl hydroxymethyl cellulose), minerals (including talc, silica, alumina, mica, and clay, the latter being represented by bentonite, hectorite, and attapulgite), magnesium aluminum silicate, and mixtures thereof. The amount of thickener may be, for example, from 0.05 to 10% by weight, more preferably from 0.3 to 2% by weight of the composition.

Preservatives may desirably be incorporated into the cosmetic compositions of the present invention to prevent the growth of potentially harmful microorganisms. Suitable conventional preservatives for use in the compositions of the present invention are alkyl esters of p-hydroxybenzoic acid. Other recently used preservatives include hydantoin derivatives, propionate salts, and a variety of quaternary ammonium compounds. Cosmetic chemists are familiar with suitable preservatives and routinely select them to meet the preservative challenge test and provide product stability. Particularly preferred preservatives are phenoxyethanol, methyl paraben, propyl paraben, butyl paraben, isobutyl paraben, imidazolidinyl urea, sodium dehydroacetate and benzyl alcohol. The preservatives should be selected having regard for the use of the composition and possible incompatibility between the preservatives and other ingredients in the composition. The preservative is preferably used in an amount of 0.01 to 2% by weight of the composition.

The composition of the present invention may also contain vitamins and flavonoids. Exemplary water-soluble vitamins are niacinamide, vitamin B2, vitamin B6, vitamin C, and biotin. Useful water-insoluble vitamins include vitamin A (retinol), vitamin A palmitate, ascorbyl tetraisopalmitate, vitamin E (tocopherol), vitamin E acetate and DL-panthenol. A particularly suitable vitamin B6 derivative is pyridoxine palmitate. Preferred flavonoids include glucosyl hesperidin and rutin. When present in the composition of the invention, the total amount of vitamins or flavonoids may for example be 0.001-10 wt%, more preferably 0.01-1 wt%, optimally 0.1-0.5 wt% of the composition.

Examples are α -hydroxycarboxylic acids and β -hydroxycarboxylic acids and salts of these acids the former include salts of glycolic, lactic and malic acids salicylic acid is representative of β -hydroxycarboxylic acids the amount of these materials when present can range from 0.1 to 15% by weight of the composition.

Various herbal extracts may optionally be included in the compositions of the present invention. Examples are pomegranate, birch (betula alba), green tea, chamomile, licorice, boswellia serrata, olive (olive) leaf, arnica, lavender and extract combinations thereof. The extract may be water soluble or water insoluble, in hydrophilic or hydrophobic solvents respectively. Water and ethanol are preferred extraction solvents.

Miscellaneous other adjunct cosmetic ingredients that may be suitable for the compositions of the present invention include ceramides (e.g., ceramide 3 and ceramide 6), conjugated linoleic acid, colorants (e.g., iron oxides), metal (manganese, copper, and/or zinc) gluconates, allantoin, palmitoyl pentapeptide-3, amino acids (e.g., alanine, arginine, glycine, lysine, proline, serine, threonine, glutamic acid, and mixtures thereof), trimethylglycine, sodium PCA, chelating agents such as disodium EDTA, opacifying agents such as titanium dioxide, magnesium aspartate, and combinations thereof. Amounts may range from 0.000001 to 3% by weight of the composition.

A small amount of emulsifying surfactant may be present. The surfactant may be anionic, nonionic, cationic, amphoteric, and mixtures thereof. The content may be, for example, 0.1 to 5% by weight, more preferably 0.1 to 2% by weight, and most preferably 0.1 to 1% by weight. Advantageously, the surfactant should be present in an amount insufficient to cause foam formation. In these cases, less than 2 wt%, preferably less than 1 wt%, and optimally less than 0.5 wt% surfactant is present. Emulsifiers such as PEG-100 stearate and emulsion stabilizers such as cetearyl alcohol and ceteareth-20 may be used and are generally used in amounts not exceeding 5% by weight of the composition.

Other optional additives suitable for use in the compositions of the present invention include cationic ammonium compounds to enhance moisturization. Such compounds include salts of hydroxypropyl tri (C1-C3 alkyl) ammonium monosubstituted saccharides, salts of hydroxypropyl tri (C1-C3 alkyl) ammonium monosubstituted polyols, dihydroxypropyl tri (C1-C3 alkyl) ammonium salts, dihydroxypropyl di (C1-C3 alkyl) mono (hydroxyethyl) ammonium salts, guar hydroxypropyl trimethylammonium salts, 2, 3-dihydroxypropyl tri (C1-C3 alkyl or hydroxyalkyl) ammonium salts, or mixtures thereof. In the most preferred embodiment and when desired, the cationic ammonium compound employed in the present invention is the quaternary ammonium compound 1, 2-dihydroxypropyltrimethylammonium chloride. Such compounds, if used, typically comprise from 0.01 to 30 weight percent of the composition, and more preferably from about 0.1 weight percent to about 15 weight percent.

When a cationic ammonium compound is used, optional additives for use therewith are humectants such as substituted ureas like methylol urea, hydroxyethyl urea, hydroxypropyl urea; bis (hydroxymethyl) urea; bis (hydroxyethyl) urea; bis (hydroxypropyl) urea; n, N' -dimethylol urea; n, N' -dihydroxyethyl urea; n, N' -dihydroxypropyl urea; n, N' -trishydroxyethyl urea; tetrakis (hydroxymethyl) urea; tetra (hydroxyethyl) urea; tetra (hydroxypropyl) urea; N-methyl-N' -hydroxyethyl urea; N-ethyl-N' -hydroxyethyl urea; N-hydroxypropyl-N '-hydroxyethyl urea and N, N' -dimethyl-N-hydroxyethyl urea or mixtures thereof. When the term hydroxypropyl appears, the meaning is a generic term for 3-hydroxy-n-propyl, 2-hydroxy-n-propyl, 3-hydroxy-isopropyl or 2-hydroxy-isopropyl. Hydroxyethyl urea is most preferred. The latter from National Starch&Chemical Division of ICI under the trade name

As 50% waterSexual liquids are available. Such substituted ureas, while desirable in moisturizing formulations, are selected for use only if they are compatible with the sunless tanning agent(s) used in the compositions of the present invention, if present.

When used, the amount of substituted urea in the compositions of the present invention ranges from 0.01 to 20%, more preferably from 0.5 to 15%, and most preferably from 2 to 10%, based on the total weight of the composition, and all ranges subsumed therein are included.

When a cationic ammonium compound and substituted urea are used, in a most particularly preferred embodiment, at least 0.01 to 25%, more preferably 0.2 to 20%, and most preferably 1 to 15%, of a humectant such as glycerin, based on the total weight of the composition, is used, and all ranges included therein are included.

When preparing the compositions of the present invention, the ingredients are typically mixed under atmospheric conditions with moderate shear. Preferably, the composition exhibits a pH of 4 to 6.

The packaging for the composition of the invention may be a can or tube as is common for cosmetic, cream, washing and lotion type products, and any other form. The composition may be applied topically, and preferably 1-4 milligrams of the composition per square centimeter of skin. The composition is preferably substantially white or colorless (transparent) in a packaged form, but may be converted to a colored composition upon application to the skin.

Methods and uses of the invention

In one aspect, the use is non-therapeutic in nature. Alternatively, it is therapeutic in nature. When the use is non-therapeutic in nature, it is preferably for cosmetic purposes.

In one aspect, the methods of the invention are non-therapeutic in nature. Alternatively, it is therapeutic in nature. When the method is non-therapeutic in nature, it is preferably used for cosmetic purposes.

The description of preferred aspects relating to the use of the composition applies mutatis mutandis to the method of the invention.

The methods of the present invention may be performed once or more times daily by application to skin in need of improved epidermal skin barrier benefits. The amount of composition used and the frequency of its administration can vary. Typically, a small amount of the composition (e.g., 0.1-5mL) is applied to the skin. A rinse step may optionally follow, depending on whether the composition is formulated as a "leave-on" or "rinse-off" product.

The invention will now be illustrated by the following non-limiting examples.

Examples

Example 1: nrf2 activation in AREc32

The source of the hydroalcoholic extract of the fruit of Phyllanthus emblica is Ihamida Phyto Life sciences P.Ltd (http:// phytoherbs. in/product. html). Which is commercially available from the supplier. The origin of emblic leafflower fruit is india. Prior to use, the extract was diluted to 0.001% with fibroblast cell culture medium as described below.

Volatile plant extracts of tea were obtained internally by following the method disclosed in US2007/0160737 a1 (Unilever). The origin of the plant is India. The extract contained E-2-hexenal and linalool in a ratio of 0.14:1 by weight parts. Before use, the extract was diluted to 0.001% using the same cell culture medium as above.

AREc32 cells were obtained from CRX biosciences (Sovidendy, England). AREc32 cells at 2X10⁴Cell/well density was seeded into 96-well plates (flat bottom white, opaque, sterile, covered) with 100. mu.L of complete medium per well. The cell plates were then incubated at 37 ℃ with 5% CO₂Next, incubation was performed in a 95% humidified incubator for 24 hours, after which the actives were added. T-butylhydroquinone (TBHQ) was used as a positive control for the assay. For Nrf2 activity assays, cells were lysed using Passive Lysis Buffer (PLB) (5X) purchased from Promega. PLB was diluted with distilled water at a ratio of 1:5 to prepare a1 XPLB solution. To each well of the 96-well plate, 20 μ L of 1X PLB was added, including 2 wells without cells (control wells). The plates were covered with aluminum foil to protect from light and incubated in a shake incubator for 20 minutes at room temperature. After 20 minutes, 18 μ Ι _ of cell lysate was transferred from a clear 96-well cell culture plate to an opaque, white, flat-bottomed 96-well plate. White flat bottom plates were subjected to luciferase assay. By usingLuciferase assay was performed using the Promega luciferase assay system. 80 μ L of luciferase reagent was added using a syringe on a TECAN infinite M1000 instrument. The time period of 10 seconds of light emission was measured using a green 1 filter. A typical delay time of 2 seconds and a read time of 10 seconds are used. 4 readings were taken from each well over 1 min. The plate is advanced to the next well to repeat the injection-then-read process. In table 1, luciferase values are expressed as fold-changes relative to controls.

TABLE 1

Note that：

Tea leaves subjected to anoxic withering (90 minutes) were also subjected to aqueous extraction and the extract was used in the experiments. It only shows a 1.86 fold increase

Tea leaves subjected to non-anoxic withering were also subjected to aqueous extraction and the extract was used in the experiments.

It only shows a 2.03-fold increase

Linalool alone shows hardly any change from the control

E-2-hexenal alone showed only 1.1 doublings relative to the control

Linalool, when combined with the plant extract of phyllanthus emblica (1mL of medium containing 500ppm of extract) in each well, showed no improvement over phyllanthus emblica alone

When combined with the plant extract of emblica officinalis in each well (1mL of medium containing 500ppm of extract), E-2-hexenal showed no improvement over emblica officinalis alone

The data in table 1 show that activation of Nrf2 was significantly higher when the two extracts were together. The data further clearly show that the overall effect is synergistic because the effect is greater than the simple arithmetic summation of their individual effects, which is predictable, and also at half the individual dose.

Example 2: HO1 expression in melanocytes

Mixing 1x 10^5HEMN (human epidermal melanin)Cell neogenesis) were plated in 12-well plates and incubated at 37 ℃ in 5% CO₂And incubated for 24 hours. The next day the actives were added and the cells were harvested after 24 hours. Total cellular RNA was extracted from these cells using the Ambion Purelink RNA mini kit (CAT # 12183020). cDNA synthesis was performed using Bio-Rad iScript (CAT # 1708891). Q PCR was then performed using specific forward (AAGACTGCGTTCCTGCTCAAC) and reverse (AAAGCCCTACAGCAACTGTCG) primers for HO 1. In our case, PCR was performed for 40 cycles in a Bio-Rad DNA Engine gradient cycler system (Bio-Rad DNA Engine gradient cycler system). Fold change was calculated using the Δ Δ cT method. (see WO2010/046316A2, Unilever). The results of the observation are listed in table 2.

TABLE 2

The data in table 2 show that the gene expression of HO1 was significantly more when the two extracts were together. The data further clearly show that the overall effect is synergistic because the effect is greater than the simple arithmetic summation of their individual effects, which is predictable, and also at half the individual dose.

Example 3: NQO1 expression in fibroblasts

1x 10^5HDFa (human dermal fibroblast maturation phase) was plated in 12-well plates and incubated at 37 ℃ with 5% CO₂And incubated for 24 hours. The next day the actives were added and the cells were harvested after 24 hours. Total cellular RNA was extracted from these cells using the Ambion Purelink RNA mini kit (CAT # 12183020). cDNA synthesis was performed using Bio-Rad iScript (CAT # 1708891). Q PCR was then performed using specific forward (GAAGAGCACTGATCGTACTGGC) and reverse (GGATACTGAAAGTTCGCAGGG) primers for NQO 1. In our case, PCR was performed for 40 cycles in a Bio-Rad DNA engine gradient cycler system. Fold change was calculated using the Δ Δ cT method. (see WO2010/046316A2, Unilever). The results of the observation are listed in table 3.

TABLE 3

The data in table 3 show that the gene expression of NQO1 was significantly more when the two extracts were together. The data further clearly show that the overall effect is synergistic because the effect is greater than the predictable simple arithmetic sum of their individual effects.

Claims

1. A topical composition comprising:

(i) a first extract comprising a plant active extracted from emblic leafflower fruit (Emblica officinalis); and

(ii) a second extract comprising volatile plant active extracted from tea (Camellia sinensis),

2. The composition of claim 1, wherein the ratio is from 0.1:1 to 5:1, parts by weight.

3. The topical composition of claim 1 or 2, wherein the plant active from emblica officinalis is extracted from its root, stem, leaf or bark by hydroalcoholic extraction.

4. The topical composition of any one of claims 1-3, wherein the first extract comprises greater than 5% ellagic acid by weight of the extract.

5. The topical composition of any one of claims 1-4, wherein the volatile plant active from tea is extracted from its leaves or fibers, or the active is contained in a fraction obtained by vacuum stripping, steam distillation, or fractionation of the volatile plant active.

6. The topical composition of any one of claims 1-5, comprising botanical actives extracted from Phyllanthus emblica in an amount of 0.001-10% by weight of the first extract.

7. The topical composition of any one of claims 1-6, comprising volatile plant active extracted from tea in an amount of 0.001-10% by weight of the second extract.

8. Use of a topical composition of any one of claims 1-7 for activating Nrf 2.

9. Use of a topical composition of any one of claims 1-8 for up-regulating the gene expression of heme oxygenase-1 (HO-1) in melanocytes.

10. Use of the topical composition of any one of claims 1-8 for up-regulating gene expression of NQO1 in fibroblasts.

11. A method of activating Nrf2, comprising the step of applying the topical cosmetic composition of any one of claims 1-8.

12. A method of up-regulating gene expression of HO1 in melanocytes comprising the step of administering a topical composition of any one of claims 1 to 8.

13. A method of up-regulating gene expression of NQO1 in fibroblasts, comprising the step of administering the topical composition of any one of claims 1-8.

14. A topical composition for activating Nrf2, comprising:

(i) a first extract comprising a plant active extracted from Phyllanthus emblica fruit, and

(ii) a second extract comprising volatile plant actives extracted from tea,

15. A topical composition for up-regulating HO1 gene expression in melanocytes comprising:

(ii) a second extract comprising volatile plant actives extracted from tea,

wherein the second extract comprises E-2-hexenal and linalool in a ratio of 0.1:1 to 10:1, parts by weight of the extract.